Engineered Cascade Components and Cascade Complexes

A composition comprising:

• a first engineered Class 1 Type I CRISPR-Cas effector complex comprising,
• a first Cas5 subunit protein and a first Cas7 subunit protein,
• a first fusion protein comprising a first Cas8 subunit protein and a first FokI, wherein the N-terminus of the first Cas8 subunit protein or the C-terminus of the first Cas8 subunit protein is covalently connected by a first linker polypeptide to the C-terminus or N-terminus of the first FokI, and wherein the first linker polypeptide has a length of between 10 amino acids to 40 amino acids, and
• a first guide polynucleotide comprising a first spacer capable of binding a first nucleic acid target sequence;
• and
• a second engineered Class 1 Type I CRISPR-Cas effector complex comprising,
• a second Cas5 subunit protein and a second Cas7 subunit protein,
• a second fusion protein comprising a second Cas8 subunit protein and a second FokI, wherein the N-terminus of the second Cas8 subunit protein or the C-terminus of the second Cas8 subunit protein is covalently connected by a second linker polypeptide to the C-terminus or N-terminus of the second FokI, and wherein the second linker polypeptide has a length of between 10 amino acids to 40 amino acids, and
• a second guide polynucleotide comprising a second spacer capable of binding a second nucleic acid target sequence, wherein a protospacer adjacent motif (PAM) of the second nucleic acid target sequence and a PAM of the first nucleic acid target sequence have an interspacer distance between 20 base pairs to 42 base pairs.